5610224 THE USE OF LUSPATERCEPT IN PATIENTS WITH β -THALASSAEMIA AND MULTIPLE SYSTEMIC COMPLICATIONS INCREASES HEMOGLOBIN LEVEL, DECREASES TRANSFUSION BURDEN, AND IS UNAFFECTED BY COMPLICATIONS. SINGLE THALASSEMIA AND SICKLE CELL DEPARTEMENT’S EXPERIENCE.
Authors: K.M. Manganas, K.A. Kotsiafti, X.A. Xydaki, D.P. Patsourakos, K.A. Aggeli, S.C. Savvidis, K.I. Koskinas, S.D. Delicou
Journal: HemaSphere (2023)

Introduction: Luspatercept is a novel recombinant protein that improves erythroid maturation and has been shown to reduce the transfusion burden in transfusion dependent β -thalassemia patients. The aim of this study is to evaluate transfusion needs, biochemical markers, and biomarkers of tissue iron overload in transfusion-dependent patients with -thalassemia and comorbidities following Luspatercept administration. Methods: In a single department of thalassemia and sickle cell disease over a 9-month period, 17 patients (Women/Men: 9/8, mean age: 50.61 years)with transfusion-dependent β-thalassemia were evaluated 12 weeks before Luspatercept administration and 12 and 24 weeks after Luspatercept administration, respectively. (image1:genotypes and cormobidities)The authors evaluated hemoglobin levels, transfusion demands, transfusion intervals, and biochemical markers. In parallel, they evaluated clinical comorbidities, liver iron content (LIC), liver fibrosis by Fibroscan, and left ventricular ejection fraction. Other treatments were provided to patients according to standard clinical practice. SPSS was used to perform statistical analysis of the results. p0.05 indicates statistical significance. Results: In three patients, the dose was increased from 1 mg to 1.25 mg/kg after three cycles of luspatercept, while in one patient there was no response and treatment discontinued. Five of the seventeen patients terminated treatment due to fatigue (4/5) and lower extremity edema (1/5). A non-statistically significant improvement in liver fibrosis and LIC was reported 24 weeks following the onset of treatment, whereas the ejection fraction improved. At 12 weeks, there was a statistically significant increase in hemoglobin levels, a decrease in blood needs, and longer intervals between transfusions. Patients continue to demonstrate statistically significant improvement in terms of improved transfusion intervals and hemoglobin levels 24 weeks after initiating therapy. Except for the increase in uric acid and LDH, the remaining biomarkers continue to improve without a statistically significant effect at 24 weeks. Ferritin levels decreased over a period of 12 to 24 weeks. There was no statistical correlation among comorbidities (pulmonary hypertension, atrial fibrillation, hypogonadism, osteoporosis, albuminuria, thrombophilia, hepatitis C, extramedullary foci) and genotypes in luspatercept response (Detailed results in table 1). Conclusions: Treatment with Luspatercept in TD patients with beta-thalassemia major and severe comorbidities has a positive effect on therapeutic efficacy. Table - of the results displaying different parameters in 17 patients pre- and post- Luspatercept administration parameter baseline 12 wks 0 to 12 wks (p<0.05) 24 wks 0 to 24 wks(p<0.05) 12 to 24 wks(p<0.05) Hb (g/dl) 10.11 11.4 <0.001 10.50 0.150 <0.001 transfused blood volume 3227 2427 <0.001 2320 0.054 <0.001 transfusion interval 15.58 21.76 <0.001 22.53 <0.001 <0.001 LIC 6.31 5.51 0,089 Fibroscan 7.57 6.82 0.093 E.F 56.59 59.53 0.011 Ferritin 1704 1204 0.139 816 0.234 0.014 LDH 311 328 0.720 412 0.263 <0.001 Uric Acid 5.5 5.7 0.421 6.38 0.28 <0.001 References 1. Cappellini, Maria Domenica, and Ali T. Taher. “The use of luspatercept for thalassemia in adults.” Blood advances 5.1 (2021): 326-333. 2. Cappellini, M. Domenica, et al. “A phase 3 trial of luspatercept in patients with transfusion-dependent β-thalassemia.” New England Journal of Medicine (2020).